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NanoMEA: A Tool for High-Throughput, Electrophysiological Phenotyping of Patterned Excitable Cells.


ABSTRACT: Matrix nanotopographical cues are known to regulate the structure and function of somatic cells derived from human pluripotent stem cell (hPSC) sources. High-throughput electrophysiological analysis of excitable cells derived from hPSCs is possible via multielectrode arrays (MEAs) but conventional MEA platforms use flat substrates and do not reproduce physiologically relevant tissue-specific architecture. To address this issue, we developed a high-throughput nanotopographically patterned multielectrode array (nanoMEA) by integrating conductive, ion-permeable, nanotopographic patterns with 48-well MEA plates, and investigated the effect of substrate-mediated cytoskeletal organization on hPSC-derived cardiomyocyte and neuronal function at scale. Using our nanoMEA platform, we found patterned hPSC-derived cardiac monolayers exhibit both enhanced structural organization and greater sensitivity to treatment with calcium blocking or conduction inhibiting compounds when subjected to high-throughput dose-response studies. Similarly, hPSC-derived neurons grown on nanoMEA substrates exhibit faster migration and neurite outgrowth speeds, greater colocalization of pre- and postsynaptic markers, and enhanced cell-cell communication only revealed through examination of data sets derived from multiple technical replicates. The presented data highlight the nanoMEA as a new tool to facilitate high-throughput, electrophysiological analysis of ordered cardiac and neuronal monolayers, which can have important implications for preclinical analysis of excitable cell function.

SUBMITTER: Smith AST 

PROVIDER: S-EPMC7547911 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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NanoMEA: A Tool for High-Throughput, Electrophysiological Phenotyping of Patterned Excitable Cells.

Smith Alec S T AST   Choi Eunpyo E   Gray Kevin K   Macadangdang Jesse J   Ahn Eun Hyun EH   Clark Elisa C EC   Laflamme Michael A MA   Wu Joseph C JC   Murry Charles E CE   Tung Leslie L   Kim Deok-Ho DH  

Nano letters 20191223 3


Matrix nanotopographical cues are known to regulate the structure and function of somatic cells derived from human pluripotent stem cell (hPSC) sources. High-throughput electrophysiological analysis of excitable cells derived from hPSCs is possible via multielectrode arrays (MEAs) but conventional MEA platforms use flat substrates and do not reproduce physiologically relevant tissue-specific architecture. To address this issue, we developed a high-throughput nanotopographically patterned multiel  ...[more]

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